@article{WincklerKruegerSchnitzleretal.2014, author = {Winckler, Silvia and Krueger, Rolf and Schnitzler, Thomas and Zang, Werner and Fischer, Rainer and Biselli, Manfred}, title = {A sensitive monitoring system for mammalian cell cultivation processes: a PAT approach}, series = {Bioprocess and biosystems engineering}, volume = {37}, journal = {Bioprocess and biosystems engineering}, number = {5}, publisher = {Springer}, address = {Berlin, Heidelberg}, issn = {1615-7591 (Print) 1615-7605 (Online)}, doi = {10.1007/s00449-013-1062-8}, pages = {901 -- 912}, year = {2014}, abstract = {Biopharmaceuticals such as antibodies are produced in cultivated mammalian cells, which must be monitored to comply with good manufacturing practice. We, therefore, developed a fully automated system comprising a specific exhaust gas analyzer, inline analytics and a corresponding algorithm to precisely determine the oxygen uptake rate, carbon dioxide evolution rate, carbon dioxide transfer rate, transfer quotient and respiratory quotient without interrupting the ongoing cultivation, in order to assess its reproducibility. The system was verified using chemical simulation experiments and was able to measure the respiratory activity of hybridoma cells and DG44 cells (derived from Chinese hamster ovary cells) with satisfactory results at a minimum viable cell density of ~2.0 × 10⁵ cells ml⁻¹. The system was suitable for both batch and fed-batch cultivations in bubble-aerated and membrane-aerated reactors, with and without the control of pH and dissolved oxygen.}, language = {en} } @article{MeyerStorkHoeckerBerndt1992, author = {Meyer-Stork, L. Sebastian and H{\"o}cker, Hartwig and Berndt, Heinz}, title = {Syntheses and reactions of urethanes of cellobiose and cellulose-containing uretdione groups}, series = {Journal of applied polymer science}, volume = {44}, journal = {Journal of applied polymer science}, number = {6}, issn = {1097-4628}, pages = {1043 -- 1049}, year = {1992}, language = {en} } @article{HemmerlingMerschenzQuackWunderlich1988, author = {Hemmerling, H.-J. and Merschenz-Quack, Angelika and Wunderlich, H.}, title = {Crystal structures of indeno[1,2-d]imidazoles. XIth European Crystallographic Meeting, Vienna 1988}, series = {Zeitschrift f{\"u}r Kristallographie - Crystalline Materials}, volume = {185}, journal = {Zeitschrift f{\"u}r Kristallographie - Crystalline Materials}, number = {H. 1-4}, issn = {2196-7105 (E-Books); 2194-4946 (Print)}, pages = {256}, year = {1988}, language = {en} } @article{AbulnagaPinkenburgSchiffelsetal.2013, author = {Abulnaga, El-Hussiny and Pinkenburg, Olaf and Schiffels, Johannes and E-Refai, Ahmed and Buckel, Wolfgang and Selmer, Thorsten}, title = {Effect of an Oxygen-Tolerant Bifurcating Butyryl Coenzyme A Dehydrogenase/Electron-Transferring Flavoprotein Complex from Clostridium difficile on Butyrate Production in Escherichia coli}, series = {Journal of bacteriology}, volume = {195}, journal = {Journal of bacteriology}, number = {16}, issn = {1098-5530 [E-Journal]}, pages = {3704 -- 3713}, year = {2013}, language = {en} } @article{SchiffelsPinkenburgScheldenetal.2013, author = {Schiffels, Johannes and Pinkenburg, Olaf and Schelden, Maximilian and Aboulnaga, El-Hussiny A. A. and Baumann, Marcus and Selmer, Thorsten}, title = {An innovative cloning platform enables large-scale production and maturation of an oxygen-tolerant [NiFe]-hydrogenase from cupriavidus necator in Escherichia coli}, series = {PLOS one. 2013}, journal = {PLOS one. 2013}, publisher = {Public Library of Science}, address = {San Francisco, California}, issn = {1932-6203}, doi = {10.1371/journal.pone.0068812}, year = {2013}, language = {en} } @article{HuckSchiffelsHerreraetal.2013, author = {Huck, Christina and Schiffels, Johannes and Herrera, Cony N. and Schelden, Maximilian and Selmer, Thorsten and Poghossian, Arshak and Baumann, Marcus and Wagner, Patrick and Sch{\"o}ning, Michael Josef}, title = {Metabolic responses of Escherichia coli upon glucose pulses captured by a capacitive field-effect sensor}, series = {Physica Status Solidi (A)}, volume = {210}, journal = {Physica Status Solidi (A)}, number = {5}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0031-8965}, doi = {10.1002/pssa.201200900}, pages = {926 -- 931}, year = {2013}, abstract = {Living cells are complex biological systems transforming metabolites taken up from the surrounding medium. Monitoring the responses of such cells to certain substrate concentrations is a challenging task and offers possibilities to gain insight into the vitality of a community influenced by the growth environment. Cell-based sensors represent a promising platform for monitoring the metabolic activity and thus, the "welfare" of relevant organisms. In the present study, metabolic responses of the model bacterium Escherichia coli in suspension, layered onto a capacitive field-effect structure, were examined to pulses of glucose in the concentration range between 0.05 and 2 mM. It was found that acidification of the surrounding medium takes place immediately after glucose addition and follows Michaelis-Menten kinetic behavior as a function of the glucose concentration. In future, the presented setup can, therefore, be used to study substrate specificities on the enzymatic level and may as well be used to perform investigations of more complex metabolic responses. Conclusions and perspectives highlighting this system are discussed.}, language = {en} } @article{WernerGroebelKrumbeetal.2012, author = {Werner, Frederik and Groebel, Simone and Krumbe, Christoph and Wagner, Torsten and Selmer, Thorsten and Yoshinobu, Tatsuo and Baumann, Marcus and Sch{\"o}ning, Michael Josef}, title = {Nutrient concentration-sensitive microorganism-based biosensor}, series = {Physica Status Solidi (a)}, volume = {209}, journal = {Physica Status Solidi (a)}, number = {5}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201100801}, pages = {900 -- 904}, year = {2012}, language = {en} } @article{BaeckerRaueSchusseretal.2012, author = {B{\"a}cker, Matthias and Raue, Markus and Schusser, Sebastian and Jeitner, C. and Breuer, L. and Wagner, P. and Poghossian, Arshak and F{\"o}rster, Arnold and Mang, Thomas and Sch{\"o}ning, Michael Josef}, title = {Microfluidic chip with integrated microvalves based on temperature- and pH-responsive hydrogel thin films}, series = {Physica Status Solidi (a)}, volume = {209}, journal = {Physica Status Solidi (a)}, number = {5}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201100763}, pages = {839 -- 845}, year = {2012}, abstract = {Two types of microvalves based on temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and pH-responsive poly(sodium acrylate) (PSA) hydrogel films have been developed and tested. The PNIPAAm and PSA hydrogel films were prepared by means of in situ photopolymerization directly inside the fluidic channel of a microfluidic chip fabricated by combining Si and SU-8 technologies. The swelling/shrinking properties and height changes of the PNIPAAm and PSA films inside the fluidic channel were studied at temperatures of deionized water from 14 to 36 °C and different pH values (pH 3-12) of Titrisol buffer, respectively. Additionally, in separate experiments, the lower critical solution temperature (LCST) of the PNIPAAm hydrogel was investigated by means of a differential scanning calorimetry (DSC) and a surface plasmon resonance (SPR) method. Mass-flow measurements have shown the feasibility of the prepared hydrogel films to work as an on-chip integrated temperature- or pH-responsive microvalve capable to switch the flow channel on/off.}, language = {en} } @article{BaeckerRakowskiPoghossianetal.2013, author = {B{\"a}cker, Matthias and Rakowski, D. and Poghossian, Arshak and Biselli, Manfred and Wagner, Patrick and Sch{\"o}ning, Michael Josef}, title = {Chip-based amperometric enzyme sensor system for monitoring of bioprocesses by flow-injection analysis}, series = {Journal of Biotechnology}, volume = {163}, journal = {Journal of Biotechnology}, number = {4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0168-1656}, doi = {10.1016/j.jbiotec.2012.03.014}, pages = {371 -- 376}, year = {2013}, abstract = {A microfluidic chip integrating amperometric enzyme sensors for the detection of glucose, glutamate and glutamine in cell-culture fermentation processes has been developed. The enzymes glucose oxidase, glutamate oxidase and glutaminase were immobilized by means of cross-linking with glutaraldehyde on platinum thin-film electrodes integrated within a microfluidic channel. The biosensor chip was coupled to a flow-injection analysis system for electrochemical characterization of the sensors. The sensors have been characterized in terms of sensitivity, linear working range and detection limit. The sensitivity evaluated from the respective peak areas was 1.47, 3.68 and 0.28 μAs/mM for the glucose, glutamate and glutamine sensor, respectively. The calibration curves were linear up to a concentration of 20 mM glucose and glutamine and up to 10 mM for glutamate. The lower detection limit amounted to be 0.05 mM for the glucose and glutamate sensor, respectively, and 0.1 mM for the glutamine sensor. Experiments in cell-culture medium have demonstrated a good correlation between the glutamate, glutamine and glucose concentrations measured with the chip-based biosensors in a differential-mode and the commercially available instrumentation. The obtained results demonstrate the feasibility of the realized microfluidic biosensor chip for monitoring of bioprocesses.}, language = {en} } @article{SpiessWilfriedAlvarezetal.2011, author = {Spiess, Elmar and Wilfried, Reichardt and Alvarez, Gerardo and Gottrup, Marcus and {\"O}hlschl{\"a}ger, Peter}, title = {An Artificial PAP Gene Breaks Self-tolerance and Promotes Tumor Regression in the TRAMP Model for Prostate Carcinoma}, series = {Molecular Therapy}, volume = {20}, journal = {Molecular Therapy}, number = {3}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {1525-0016}, pages = {555 -- 564}, year = {2011}, language = {en} } @article{LeursMezoOehlschlaegeretal.2012, author = {Leurs, Ulrike and Mezo, Gabor and {\"O}hlschl{\"a}ger, Peter and Orban, Erika and Marquard, Andrea and Manea, Marilena}, title = {Design, synthesis, in vitro stability and cytostatic effect of multifunctional anticancer drug-bioconjugates containing GnRH-III as a targeting moiety}, series = {Peptide Science}, volume = {98}, journal = {Peptide Science}, number = {1}, publisher = {Wiley}, address = {New York, NY}, issn = {1097-0282}, doi = {10.1002/bip.21640}, pages = {1 -- 10}, year = {2012}, abstract = {Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.}, language = {en} } @article{ManeaLeursOrbanetal.2011, author = {Manea, Marilena and Leurs, Ulrike and Orban, Erika and Baranyai, Zsuzsa and {\"O}hlschl{\"a}ger, Peter and Marquardt, Andreas and Schulcz, Akos and Tejeda, Miguel}, title = {Enhanced Enzymatic Stability and Antitumor Activity of Daunorubicin-GnRH-III Bioconjugates Modified in Position 4}, series = {Bioconjugate Chemistry}, volume = {22}, journal = {Bioconjugate Chemistry}, number = {7}, publisher = {ACS}, address = {Washington, DC}, isbn = {1520-4812}, pages = {1320 -- 1329}, year = {2011}, language = {en} } @article{ImmelGrothHuhnetal.2011, author = {Immel, Timo A. and Groth, Ulrich and Huhn, Thomas and {\"O}hlschl{\"a}ger, Peter}, title = {Titanium salan complexes displays strong antitumor properties in vitro and in vivo in mice}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {3}, publisher = {Plos}, address = {San Francisco, California, US}, doi = {10.1371/journal.pone.0017869}, pages = {e17869}, year = {2011}, abstract = {The anticancer activity of titanium complexes has been known since the groundbreaking studies of K{\"o}pf and K{\"o}pf-Maier on titanocen dichloride. Unfortunately, possibly due to their fast hydrolysis, derivatives of titanocen dichloride failed in clinical studies. Recently, the new family of titanium salan complexes containing tetradentate ONNO ligands with anti-cancer properties has been discovered. These salan complexes are much more stabile in aqueous media. In this study we describe the biological activity of two titanium salan complexes in a mouse model of cervical cancer. High efficiency of this promising complex family was demonstrated for the first time in vivo. From these data we conclude that titanium salan complexes display very strong antitumor properties exhibiting only minor side effects. Our results may influence the chemotherapy with metallo therapeutics in the future.}, language = {en} } @article{OehlschlaegerQuettingAlvarezetal.2009, author = {{\"O}hlschl{\"a}ger, Peter and Quetting, Michael and Alvarez, Gerardo and D{\"u}rst, Matthias and Gissmann, Lutz and Kaufmann, Andreas M.}, title = {Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants}, series = {International Journal of Cancer}, volume = {125}, journal = {International Journal of Cancer}, number = {1}, publisher = {Wiley}, address = {Weinheim}, isbn = {1097-0215}, pages = {189 -- 198}, year = {2009}, language = {en} } @article{OosterhuisOehlschlaegerBergetal.2011, author = {Oosterhuis, Koen and {\"O}hlschl{\"a}ger, Peter and Berg, Joost H. van den and Toebes, Mireille and Gomez, Raquel and Schumacher, Ton N. and Haanen, John B.}, title = {Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7}, series = {International Journal of Cancer}, volume = {129}, journal = {International Journal of Cancer}, number = {2}, publisher = {Wiley}, address = {Weinheim}, isbn = {1097-0215}, pages = {397 -- 406}, year = {2011}, language = {en} } @article{OehlschlaegerSpiesAlvarezetal.2011, author = {{\"O}hlschl{\"a}ger, Peter and Spies, Elmar and Alvarez, Gerardo and Quetting, Michael and Groettrup, Marcus}, title = {The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA}, series = {International Journal of Cancer. 128 (2011), H. 2}, journal = {International Journal of Cancer. 128 (2011), H. 2}, publisher = {Wiley}, address = {Weinheim}, isbn = {1097-0215}, pages = {473 -- 481}, year = {2011}, language = {en} } @article{OehlschlaegerOsenDelletal.2003, author = {{\"O}hlschl{\"a}ger, Peter and Osen, Wolfram and Dell, Kerstin and Faath, Stefan}, title = {Human papillomavirus type 16 L1 capsomeres induce L1-specific cytotoxic T lymphocytes and tumor regression in C57BL/6 mice / {\"O}hlschl{\"a}ger, Peter ; Osen, Wolfram ; Dell, Kerstin ; Faath, Stefan ; Garcea Robert L: ; Jochmus, Ingrid ; M{\"u}ller, Martin, Pawlita,}, series = {Journal of Virology. 77 (2003), H. 8}, journal = {Journal of Virology. 77 (2003), H. 8}, isbn = {1098-5514}, pages = {4635 -- 4645}, year = {2003}, language = {en} } @article{OehlschlaegerCorvinusOrthetal.2005, author = {{\"O}hlschl{\"a}ger, Peter and Corvinus, Florian M. and Orth, Carina and Moriggl, Richard}, title = {Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth / Corvinus, Florian, Moriggl, Richard ; Tsareva, Svetlana A. ; Wagner, Stefan ; Pfitzner, Edith B. ; Baus, Daniela ; Kaufmann, Roland : Huber, Luka}, series = {Neoplasia. 7 (2005), H. 6}, journal = {Neoplasia. 7 (2005), H. 6}, isbn = {1476-5586}, pages = {545 -- 555}, year = {2005}, language = {en} } @article{OehlschlaegerMichelOsenetal.2002, author = {{\"O}hlschl{\"a}ger, Peter and Michel, Nico and Osen, Wolfram and Freyschmidt, Eva-Jasmin}, title = {T cell response to human papillomavirus 16 E7 in mice: comparison of Cr release assay, intracellular IFN-gamma production, ELISPOT and tetramer staining / Michel, Nico ; {\"O}hlschl{\"a}ger, Peter ; Osen, Wolfram ; Freyschmidt, Eva-Jasmin ; Gut{\"o}hrlein, Heidrun ;}, series = {Intervirology. 45 (2002)}, journal = {Intervirology. 45 (2002)}, isbn = {1423-0100}, pages = {290 -- 299}, year = {2002}, language = {en} } @article{OehlschlaegerSteinbergSehretal.2005, author = {{\"O}hlschl{\"a}ger, Peter and Steinberg, Thorsten and Sehr, Peter and Osen, Wolfram}, title = {Modification of HPV 16 E7 genes: correlation between the level of protein expression and CTL response after immunization of C57BL/6 mice / Steinberg, Thorsten ; {\"O}hlschl{\"a}ger, Peter ; Sehr, Peter ; Osen, Wolfram ; Gissmann, Lutz}, series = {Vaccine. 23 (2005), H. 9}, journal = {Vaccine. 23 (2005), H. 9}, isbn = {0264-410X}, pages = {1149 -- 1157}, year = {2005}, language = {en} }